Interaction of Cisplatin with Human Superoxide Dismutase

cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. It also binds to Cu2–Zn2 and Zn2–Z...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2012-04, Vol.134 (16), p.7009-7014
Main Authors: Banci, Lucia, Bertini, Ivano, Blaževitš, Olga, Calderone, Vito, Cantini, Francesca, Mao, Jiafei, Trapananti, Angela, Vieru, Miguela, Amori, Ilaria, Cozzolino, Mauro, Carrì, Maria Teresa
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cisplatin - chemistry
Cisplatin - pharmacology
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Humans
Mice
Models, Molecular
Solutions
Structure-Activity Relationship
Superoxide Dismutase - antagonists & inhibitors
Superoxide Dismutase - chemistry
Superoxide Dismutase - metabolism
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Summary:cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. It also binds to Cu2–Zn2 and Zn2–Zn2 forms of hSOD1. Cisplatin inhibits aggregation of demetalated oxidized hSOD1, and it is further able to dissolve and monomerize oxidized hSOD1 oligomers in vitro and in cell, thus indicating its potential as a leading compound for amyotrophic lateral sclerosis.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja211591n